Basic Science and Pathogenesis.

Background: Although the rate of Alzheimer's disease (AD) in African-ancestry (AA) Americans is higher than that of persons from European-ancestry (EA) populations, AA participants have been underrepresented in AD neuropathological studies.

Method: Utilizing the AD Research Centers (ADRC) infrastructure, we obtained AA donor pre-frontal cortex (PFC) tissue from brain repositories of 12 ADRC and generated bulk RNA sequencing (RNA-seq) data for 179 samples that met QC and inclusion criteria. Previously generated PFC RNAseq data were obtained for 28 additional AA donors from the Columbia University ADRC.

Widespread perturbation of ETS factor binding sites in cancer.

Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a transcription factor (TF)-aware burden test based on a model of coherent TF function in promoters. We apply this test to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predict 2555 driver NCVs in the promoters of 813 genes across 20 cancer types.

Functional genome-wide short hairpin RNA library screening identifies key molecules for extracellular vesicle secretion from microglia.

Activated microglia release extracellular vesicles (EVs) as modulators of brain homeostasis and innate immunity. However, the molecules critical for regulating EV production from microglia are poorly understood. Here we establish a murine microglial cell model to monitor EV secretion by measuring the fluorescence signal of tdTomato, which is linked to tetraspanin CD63.